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38 (); 73-78
doi:
10.1016/j.jor.2023.03.010

Creatine supplementation in the pediatric and adolescent athlete-- A literature review

, , , ,
a Center for Surgical Outcomes Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA
b Nationwide Children's Hospital Library, Columbus, OH, USA
c Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, OH, USA

∗Corresponding author: Kevin E. Klingele. Kevin.Klingele@nationwidechildrens.org

Received: , Accepted: ,
Professor P K Surendran Memorial Education Foundation
Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Abstract

An increase in intra-muscular creatine through supplementation has been proposed as a strategy for improving muscle performance and recovery, with studies showing some benefit for adult athletes who rely on short, explosive movements. We reviewed and summarized the current literature on creatine supplementation in a pediatric and adolescent population.

The databases PubMed and EMBASE were queried to identity articles related to the use of creatine supplementation in a healthy pediatric and adolescent population according to the guidelines established by PRISMA. The abstracts of all articles were reviewed to determine relevancy, with those meeting the pre-defined criteria included in the final review.

A combined total of 9393 articles were identified. Following application of filters and review of abstracts, 13 articles were found to meet criteria and were included in the final review. There was a total of 268 subjects across all studies, with mean age ranging from 11.5 to 18.2 years. More than 75% of the studies were randomized-controlled trials, and 85% involved either soccer players or swimmers. The overall quality of the studies was poor, and there were no consistent findings regarding creatine supplementation and improvements in athletic performance. No studies were designed to address the topic of safety.

There is a gap in the study of the safety and efficacy of creatine supplementation in adolescents. Additional studies are needed to evaluate the effects of alterations in muscle composition on the growth, development, and performance of the developing athlete. Orthopedic providers should counsel their pediatric and adolescent patients on the current limitations in trying to assess the true risk and benefit of creatine supplementation for the aspiring athlete.

Review, III.

Keywords

Creatine
Supplementation
Adolescents
Performance
Outcomes
1

1 Introduction

The bioactive form of creatine is found in high concentration within skeletal muscle, where it acts as a store of adenosine-triphosphate (ATP) and provides a readily available energy source to aid in the early phases of muscle activation.1 Absent or severely diminished levels of creatine are typically only found in patients with rare genetic disorders but can lead to devastating abnormalities in development without early detection and treatment.2 In a healthy population, creatine is synthesized naturally by the liver and kidney, with most individuals able to maintain sufficient levels through diet. An insufficiency in creatine has been hypothesized to lead to an increased risk for myopathy, however, this relationship has not been adequately studied and the long-term consequences of marginally decreased levels remains unknown.3 It is estimated that non-athletes must consume 1–2 g of creatine per day as part of their diet, compared to 5–10 g per day for athletes in training.4 At equilibrium, creatine stores in the body are 60–80% saturated, but higher levels of intra-muscular creatine concentrations can be obtained through supplementation.1 Achieving supraphysiologic levels of intra-muscular creatine has been proposed as a mechanism to improve muscle performance and recovery through increased neuromuscular synthesis and augmentation of the muscle's metabolic capacity.5,6 Based on this assumption, research on the use of creatine as a dietary supplement grew considerably in the early 2000s.7,8 Studies evaluating the effect of creatine on muscle have found that a short-term supplementation regimen of 5–7 days is sufficient to increase muscle volumes by 10–20%, however, the implications of these changes have not been fully elucidated.1

Research on the effect of creatine on muscle recovery and sport-specific performance remains scarce. To date, studies on the safety and efficacy of creatine supplementation on athletic performance have been limited mostly to adult populations.7,9–11 For adult athletes, creatine use has been linked to an increase in performance over baseline in sports that rely on fast-twitch muscle action, such as sprinting, short distance swimming, and sprint cycling.7,12,13 In healthy adults, creatine supplementation has also been proposed as an adjunct to aid recovery and is associated with a low risk of adverse events, with the most common side effects being weight gain, muscle cramps, and gastrointestinal discomfort.4,9,10,14–16 Despite a growing breadth of literature on the use of creatine in an adult population, the studies to date have not been adequately powered nor appropriately designed to decisively prove the creatine has an effect on performance in adults. Although limited, research on creatine use in adults does indicate that creatine supplementation is safe and that it may provide potential benefit to athletes, however, little is known about the efficacy and safety in children and adolescent populations. Creatine is the most commonly used supplement by collegiate athletes across the United States, with use ranging from 13 to 30% depending on the sex and sport of the athlete.4 With an increased prevalence in year-round, sport-specific training among young athletes over the past several decades, it is not surprising that creatine use has been reported in grade school athletes and up to 40% of senior-level high school athletes.17–19 The objectives of this review were: 1) to summarize the available literature on the use of creatine supplementation in pediatric and adolescent athletes, 2) to describe the safety and effects of creatine supplementation on performance, and 3) to identify gaps in the literature on the study of creatine use in this population.

2

2 Methods

2.1

2.1 Study design

The study was designed according to the standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).20 Scoping reviews provide a standardized approach for identifying and reporting the quality and potential gaps in the current literature for topics that may not meet the criteria necessary to carry out a systematic review.21

2.1.1

2.1.1 Database inquiry

In February 2021, in order to answer the authors’ question “what are the effects of creatine in adolescents?“, a research librarian (AG) conducted a search using PRISMA guidelines and the databases PubMed and EMBASE. The broad search term used was “creatine” in MeSH as well as in natural language to search PubMed. In Embase, the term “creatine” was exploded to include:'(alpha methylguanido) acetic; ‘creatine’; ‘creatine hydrate’; ‘creatine monohydrate’; ‘methylglycocyamine’; ‘methylguanidoacetic acid’; ‘n amidinosarcosine’; n guanyl n methylglycine’; as well as ‘n methyl n guanylglycine’. The search was meant to be as inclusive as possible and therefore included both the specific keyword and synonyms. To target the search to our desired population, the dataset was limited by age (0–18 years) and inclusive of original research designs including randomized control trials, clinical trials, and other forms of trials where hard data could be extracted. Article types such as case studies, systematic reviews, reviews, and editorials, were excluded.

2.2

2.2 Article screening and data extraction

A consensus list of eligibility criteria was created prior to the literature search. Articles were considered eligible for inclusion if the study design was either limited to patients aged less than 18 years or included a sub-analysis of this population, if the tested hypothesis included creatine supplementation, and if there was at least one measure of an outcome associated with creatine supplementation (either positive or deleterious). Review and opinion articles were excluded, as were articles that had a study design focused on adults or patients with disease.

Two authors independently reviewed all articles that were returned from the database inquiry for inclusion, with any discrepancies mediated by a third author. Duplicate articles were removed, and qualifying articles then read in their entirety, with appropriate data extracted and stored on a shared network. All references were housed in EndNote (Clarivate, Philadelphia, PA).

3

3 Results

3.1

3.1 Search results

The initial search yielded 685 articles from PubMed and 8708 articles from EMBASE. After applying the appropriate filters, the refined search yielded 70 articles from PubMed and 60 from EMBASE. Following removal of duplicates, a total of 13 articles met the pre-defined criteria and were included in the final review (Fig. 1).

Article Selection A search of the databases PubMed and EMBASE identified 9393 articles related to the use of creatine supplementation in a pediatric population. However, following review of the abstracts, only 12 articles were found to be appropriate for inclusion in the final review.
Fig. 1 Article Selection A search of the databases PubMed and EMBASE identified 9393 articles related to the use of creatine supplementation in a pediatric population. However, following review of the abstracts, only 12 articles were found to be appropriate for inclusion in the final review.
3.2

3.2 Study characteristics

Table 1 provides a summary of all articles that were included in the final review. The date of publication ranged from 2002 to 2019, and there was a total of 268 subjects across all studies, with a mean age ranging from 11.5 to 18.2 years. The most common study was a randomized controlled trial (RCT; 77%), and all but one study focused on the physical performance of athletes (93%).

Table 1 Included studies.
Year Authors Type Population N (% Male) Mean Age (years) Control Group Measure of Performance Effect of Creatine Supplementation Creatine Regimen
2019 da Silva Azevedo et al. Cross-over single-blind Soccer players 8 (100) 16.3 ± 0.5y Placebo Magnitude and time to generation of first peak in muscle activation Decreased magnitude of and increased time to first peak in muscle activation. 0.3 g/kg/d x 7 days
Loading rate/Impulse during first 50 ms No difference in other measures.
2002 Dawson et al. Prospective Cohort Swimmers 20 (10) 16.4 ± 1.8y Placebo Plasma lactate Improvement in work output 20g × 5 days then 5g × 22 days
Sprint swim speed No difference in swim speed, BMI, or plasma lactate
Work output
BMI
2016 Deminice et al. RCT Soccer players 13 (100) 18.2 ± 0.8y Placebo Total body water and mass Cr group gained more water and mass than placebo group, with average of 2.3 L of body water and 1.0 kg of mass. 0.3 g/kg/d x 7d
2013 Deminice et al. Cross-over Soccer players 23 (100) 17.6 ± 0.5 y Placebo Plasma Cr, guanidinoacetic acid, and homocysteine levels after sprint exercise No difference in post-sprint homocysteine plasma levels 0.3 g/kg/d x 7 days
2018 Juhàsz et al. RCT Injured fin swimmers 18 (55.6) 15.1 ± 1.4y Placebo Segmental lean mass (SLM) Significantly greater SLM in Cr group following immobilization and rehabilitationSignificantly greater PFT More rapid improvement in pain scores No difference in CK 20g × 5 days and then 5g × 37 days
Plantar flexion torque (PFT)
Creatine kinase (CK)
Pain Score
* during immobilization and rehabilitation phases of recovery
2009 Juhàsz et al. RCT Fin swimmers 15 (100) 15.9 ± 1.6y Placebo Anthropomorphic measures Increase in PO of 20% Decreased swim time Significant Increase in body mass of 1.7% Decrease in plasma lactate 20g/day x 5 days
Power output (PO)
Swimming time in 100 m fin swim
Plasma Lactate after exercise
2017 Merege-Filho et al. RCT Healthy children 67 (38) Cr: 11.5 ± 0.8y Placebo Standardized cognitive tests No difference in the change in test scores between Cr and placebo groups 0.3 g/kg x 7 days
Placebo: 11.6 ± 0.9y Brain creatine levels
2004 Ostojic et al. RCT Soccer players 21 (100) 16.6 ± 1.9y Placebo Dribble time Dribble, vertical jump and sprint-power performance improved in the Cr group, with all 3 measures superior in Cr group compared to placebo 30g × 7 days
Sprint-power time
Endurance test
Vertical jump
2007 Silva et al. RCT Swimmers 16 (0) 16.3 ± 1.8y Placebo Velocity No reported difference compared to placebo 20g/day x 21 days
Active drag force
Hydrodynamic coefficient
Power output
(during 25 m swim)
2019 Simpson et al. RCT Soccer players 19 (100) 17.4 ± 1.6y Placebo Fractional Exhalation of nitrous oxide No statistical differences between the groups 0.3 g/kg/d x 7 days then 7 weeks of 5g/day
Spirometry
Eucapnic voluntary hyperpnoea
2005 Theodorou et al. RCT Swimmers 10 (60) 17.8 ± 1.8y Creatine + 500 mL of 18.5% carbohydrate drink Swimming velocity during 50 or 100-m swims Significant increase in velocity in both groups, with no difference between groups 25g × 4 days
2017 Wang et al. RCT Canoeists 19 (100) Cr: 16.8 ± 0.7y Placebo Maximum upper body muscle strength Significantly greater maximum muscle strength 5g/day x 6 days
Placebo: 16.4 ± 1.1y Overhead medicine ball throw
Post-activation potentiation time No difference in other measures
2017 Yañez-Silva RCT Soccer players 19 (100) 17.0 ± 0.5y Placebo Peak power output (PPO) Cr group experienced significant increases in PPO, MPO, and TW; but only TW was different between Cr and placebo groups 0.03 g/kg x 14 days
Mean power output (MPO)
Total work (TW)

The most common regimen for creatine supplementation loading was 0.3 g per kilogram (g/kg) per day for 7 days (39%), followed by a regimen that included a fixed dose of 20 g per day (23%). Only 4 of 13 studies (31%) included a maintenance regimen for creatine supplementation, with the reported protocols each using a fixed dose of 5 g per day for a period ranging from 22 to 49 days.

3.3

3.3 The effects of creatine supplementation in adolescents

A single study explored the effect of creatine on the healthy, non-athlete. A study by Merege evaluating cognitive function in children aged 10–12 years found no differences in standardized test scores either between groups or across members of the same group when comparing subjects who either received creatine supplementation or placebo for 1 week.22

Studies exploring the effect of creatine supplementation on performance for adolescent athletes in training were limited mainly to two sports, soccer and swimming. Among soccer players, studies showed a generally positive relationship between creatine supplementation and performance. Using a cross-over design, da Silva Azevedo compared the effects of creatine supplementation to placebo on the muscle activation and force generation of elite soccer players when performing high-intensity training, as measured by parameters related to the first peak in force generation and muscle activation across 5 lower limb muscles. The group found a trend toward a decreased magnitude of the first peak and an increased time to first peak for the creatine group, which they hypothesized may lead to an improvement in recovery through decreased impact on the muscles during intensive training.23 Yañez-Silva and colleagues evaluated peak power output (PPO), mean power output (MPO), total work (TW), and fatigue index (FI) for soccer players performing the Wingate anaerobic test after supplementation with either creatine or placebo for 14 days. There were no differences in fatigue for either group. The creatine group experienced a significant increase in PPO, MPO, and TW from pre-to post-supplementation; however, there was only a significant difference between the creatine and placebo groups for TW.24 Ostojic designed a study to evaluate the effects of creatine supplementation on soccer-specific skills, finding that a 7-day regimen led to improvements in dribble time, power-sprint performance, and vertical jump and that there was a significant difference between the creatine and placebo groups for each performance variable.25

The relationship between creatine supplementation and swimming performance was more varied. In one study by Juhàsz, when compared to placebo, creatine supplementation was associated with an increase in power output, an improved 100-m swim time, and a decrease in post-exercise plasma lactate levels following a dedicated training program.26 There was also a significant gain in mass among the creatine group that was not present in the placebo group. In a separate study by Juhàsz examining the effects of creatine on injured fin swimmers during the immobile and rehabilitative phases of recovery found supplementation to lessen muscle wasting during the period of disuse and also to be associated with greater plantar flexion torque and muscle growth during rehabilitation as well as a more rapid improvement in pain scores, although there was no difference in plasma creatine kinase levels following training.27 Theordorou and colleagues did not use a placebo group for comparison but did report an increase in swimming velocity following 4 days of creatine supplementation, with no difference in performance found with the addition of a carbohydrate beverage during creatine ingestion.28 In contrast to the above authors, Silva and colleagues reported no difference in swimming velocity or power output between creatine and placebo groups during a 25-m swim following 21 days of supplementation.29 Similarly, Dawson found no difference in sprint swim speed following 27 days of creatine supplementation despite an increase in the measured work output.30 In the only study evaluating performance in a group that did not include soccer players or swimmers, Wang showed that 6 days of creatine supplementation led to an increase in maximum upper body muscle strength for high school canoeists, with no difference in explosive power or post-activation muscle potentiation time.31

3.4

3.4 The safety of creatine supplementation

No studies were designed to explore the adverse effects of creatine supplementation in adolescents. However, two studies by Deminice were performed to explore the relationship between creatine supplementation and markers of physiologic change. The group found that following a 7 day regimen, soccer players who supplemented with creatine experienced an average gain in total body water of more than 2.3 L and an associated gain in total body weight of 1 kg, both of which were significantly greater than the changes seen in the placebo group.32 In a separate study by the same group exploring soccer players following sprint exercise, creatine supplementation did not affect the plasma levels of homocysteine, a proposed risk factor for cardiovascular disease.33 A study by Simpson designed to evaluate the effect of creatine supplementation on measures of lung performance failed to show a difference between control and treatment groups; however, there was a trend among the creatine group toward unfavorable changes in the fractional excretion of nitrous oxide, which was greater in a subset of patients with atopic dermatitis.34

4

4 Discussion

Although creatine appears safe for short-term supplementation, additional studies are needed to reliably answer questions regarding the long-term risks and benefits of use across a diverse population of pediatric and adolescent participants. The studies included in this review suggest that creatine supplementation has the potential to improve performance for adolescent athletes. However, to date, the research exploring the connection between creatine use and athletic performance is lacking the appropriate power to reliably ascertain a relationship between creatine supplementation and performance in young athletes. The paucity of high-quality research uncovered in this review prohibit the extraction of meaningful conclusions regarding a relationship between creatine supplementation and physical performance in an adolescent population.

Before considering the potential benefit of supplementation on performance, it is important to first understand the safety profile associated with using creatine in a non-adult population. Early reports describing cases of kidney injury following creatine use led to concern that supplementation could lead to nephrotoxicity. However, it was later discovered that the isolated cases were largely confounded by an underlying kidney disease or the concurrent use of other substances with known nephrotoxic effects.1 Several studies have since shown that creatine supplementation can result in a transient rise in plasma creatine levels but that it is not associated with renal or liver injury in healthy individuals.15,35–38

With concerns regarding acute toxicity largely alleviated, it is important to consider the potential for latent adverse effects of creatine supplementation, including the impact on muscle health and development. In contrast to adults, who maintain a relatively stable skeletal muscle mass in absence of disease, healthy adolescents will experience a rapid growth in lean muscle around the time of puberty.39 Creatine supplementation is associated with a rise in intra-muscular water and can lead to increases in muscle volume and total body mass. Studies have correlated the increased muscle mass with the potential for improved strength, but the long-term sequela of an increase in skeletal muscle volume during a time of physiologic growth in adolescence remains unknown.40,41 Compared to adults, children and adolescents are at an increased risk of developing sport-related injury due in part to the changes that occur as part of the typical growth and development cycle.42,43 Although creatine supplementations do not appear to affect training-related plasma lactate levels, which have been correlated with muscle damage in the acute phase, little is known about the effect of an artificial increase in muscle mass on joint mechanics and core stability.44,45 The current literature lacks the longitudinal studies that would be necessary to best define the risk associated with creatine supplementation in adolescence, and the potential of artificial muscle growth exacerbating any deleterious effects related to changes in body composition warrants further investigation.

Creatine supplementation has been proposed as a tool to improve athletic performance though improvements in muscle efficiency and recovery following strenuous activity, with some speculation that there can be cognitive benefits as well.46,47 Although exogenous creatine has been shown to increase muscle volume and has been associated with a marginal improvement in performance for some adult athletes, the results of this review show that there is no evidence to support supplementation as effective strategy to consistently improve athletic performance in an adolescent population.48,49 In adults, studies evaluating the effects of creatine use on sport-specific performance have produced mixed results.7,50 Short-term supplementation has been associated with an increase in single measures of strength, such as bench press and torque generation, and there is some evidence to suggest a marginal benefit for adult athletes who rely on quick, explosive movements.8,51,52 However, studies have failed to identify a benefit for creatine over placebo in achieving long-term strength gains, with some evidence even suggesting a deleterious effect for athletes participating in endurance sports.7,48,53,54

Like many adult studies, research on the effect of creatine supplementation on performance for adolescent athletes has been affected by a lack of variety and small population size. The interpretation of results obtained from the study of adolescents is further complicated by the difficulty in controlling for confounding factors at the individual level, which may be more prevalent in this population due to differences in the rate of maturation and the associated variation in physical and cognitive development. To date, studies on creatine supplementation in adolescents have primarily grouped subjects based on body mass index or sex, neither of which are proven methods to control for the differences in physical and cognitive ability that exist across a developing population at baseline. The necessary components for success in athletics extend beyond physical characteristics and likely include a combination of physical and mental attributes as well as training and persistence.55–57 Previous attempts at predicting athletic talent have failed to identify a consensus regarding the importance of a single measure of physical ability; yielding instead a variety of potential physical, genetic, and mental attributes that likely all play a role in creating an opportunity to maximize athletic performance.58,59 For the adolescent athlete, increased levels of creatine can affect body mass and may help to improve muscle-specific metrics during training, but there is no evidence to support supplementation as a means to consistently improve athletic performance. Future studies are needed to identify the types of adolescent athletes that are likely to be benefit from creatine use and to define the role of supplementation in the context of a training protocol designed to help adolescents reach their personal performance goals.

5

5 Conclusions

The results of this review highlight the gap that exists on the study of creatine use in adolescents and point to the need for high-quality research to explore the effects of supplementation in a pre-adult population. Concerns regarding the risk of acute, adverse effects in a healthy population have largely been eliminated, but the long-term effects of use during a period of physiologic change remain unknown. Additional studies are needed to further evaluate the effects of alterations in muscle composition on the growth, development, and performance of the developing athlete. In the meantime, providers should counsel their pediatric and adolescent patients on the current limitations in trying to assess the true risk and benefit of creatine supplementation for the aspiring athlete.

Funding information

The authors received no funding for this study.

Informed consent

Not required for a literature review.

Institutional ethical committee approval

Not required for a literature review.

Ethical approval

Not required by the Institutional Review Board of Nationwide Children's Hospital.

Author contributions

Study conception and design: GAM, PMM, AG, KEK.

Data acquisition: GAM, AG, PMM, AD.

Analysis and data interpretation: GAM, PMM, KEK, AD.

Drafting of the manuscript: GAM, PMM, KEK, AD.

Critical Revisions: All authors.

Patient involvement statement

This is a review of the literature and did not involve patient contact.

Data sharing statement

All data relevant to the study are included in the article or are available as supplementary files. Please ensure that no patient-identifiable data are available.

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